Abstract
Introduction: LpPLA2 activity increases in inflamed plaques associated with atherosclerotic disease. Elevated circulating LpPLA2 is associated with increased risk of cardiovascular disease but it is not known whether this risk is consistent across demographic and risk groups. Methods: We developed a case cohort study within the REasons for Geographic and Racial Disparities in Stroke (REGARDS) study. We included a random cohort sample (n=3719) derived from the 23,019 REGARDS participants who were free from stroke and cardiovascular disease at baseline in 2003-7. We used weighted Cox models to study the association between LpPLA2 activity and risk of cardiovascular disease. Acute CHD during complete follow up through 12/31/2010 was adjudicated by an expert committee and defined as definite or probable myocardial infarction (MI) not resulting in death within 28 days (nonfatal acute CHD) or fatal acute CHD. LpPLA2 activity was measured using the PLAC® Activity Test at Diadexus. LpPLA2 activity was dichotomized at the 80th percentile of gender specific activity. The cut-off for men was 250 and for women was 200 nmol/ml/min. Results: The cohort included black (46%) and white (54%) participants over age 45 and was 42% male. 565 cases of acute CHD were available for analysis. After controlling for race, age, sex, statin use, income, education, lipid profile, hypertension, diabetes, and history of smoking, elevated LpPLA2 activity was associated with increased risk of cardiovascular disease HR=1.52; 95% CI (1.21, 1.91). This result was consistent and not significantly different across demographic and risk categories (Table).The Net Reclassification Index was 13%, p<0.001. Conclusions: LpPLA2 activity is associated with increased risk of cardiovascular disease among black and white men and women. The increased risk is observed even in participants at low risk of cardiovascular disease as defined by the Framingham risk function.
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